文章：

c-MYC与MYCN在神经母细胞瘤中具有预后预测价值的靶基因在交感肾上腺发育过程中呈现差异表达

Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development

原文发布日期：16 September 2023

DOI: 10.3390/cancers15184599

类型: Article

开放获取: 是

英文摘要：

Deregulation of the MYC family of transcription factors c-MYC (encoded byMYC), MYCN, and MYCL is prevalent in most human cancers, with an impact on tumor initiation and progression, as well as response to therapy. In neuroblastoma (NB), amplification of theMYCNoncogene and over-expression ofMYCcharacterize approximately 40% and 10% of all high-risk NB cases, respectively. However, the mechanism and stage of neural crest development in which MYCN and c-MYC contribute to the onset and/or progression of NB are not yet fully understood. Here, we hypothesized that subtle differences in the expression of MYCN and/or c-MYC targets could more accurately stratify NB patients in different risk groups rather than using the expression of eitherMYCgene alone. We employed an integrative approach using the transcriptome of 498 NB patients from the SEQC cohort and previously defined c-MYC and MYCN target genes to model a multigene transcriptional risk score. Our findings demonstrate that defined sets of c-MYC and MYCN targets with significant prognostic value, effectively stratify NB patients into different groups with varying overall survival probabilities. In particular, patients exhibiting a high-risk signature score present unfavorable clinical parameters, including increased clinical risk, higher INSS stage,MYCNamplification, and disease progression. Notably, target genes with prognostic value differ between c-MYC and MYCN, exhibiting distinct expression patterns in the developing sympathoadrenal system. Genes associated with poor outcomes are mainly found in sympathoblasts rather than in chromaffin cells during the sympathoadrenal development.

摘要翻译： 

MYC家族转录因子c-MYC（由MYC基因编码）、MYCN和MYCL的失调在大多数人类癌症中普遍存在，对肿瘤的发生、进展以及对治疗的反应均产生影响。在神经母细胞瘤（NB）中，MYCN原癌基因的扩增和MYC的过表达分别约占所有高风险NB病例的40%和10%。然而，MYCN和c-MYC在神经嵴发育中的具体作用机制及阶段，以及它们如何促进NB的发生和/或进展，目前尚未完全阐明。本研究假设，与单独使用任一MYC基因的表达相比，MYCN和/或c-MYC靶基因表达的细微差异可能更准确地用于将NB患者分层至不同的风险组。我们采用了一种整合方法，利用SEQC队列中498例NB患者的转录组数据以及先前定义的c-MYC和MYCN靶基因，构建了一个多基因转录风险评分模型。我们的研究结果表明，具有显著预后价值的c-MYC和MYCN靶基因集合能够有效将NB患者分层为不同组别，这些组别具有不同的总生存概率。特别是，表现出高风险特征评分的患者具有不利的临床参数，包括较高的临床风险、更高的INSS分期、MYCN扩增以及疾病进展。值得注意的是，具有预后价值的靶基因在c-MYC和MYCN之间存在差异，并在发育中的交感肾上腺系统中表现出不同的表达模式。在交感肾上腺发育过程中，与不良预后相关的基因主要存在于交感母细胞中，而非嗜铬细胞中。

原文链接：

Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development